Safety of two-year caloric restriction in non-obese healthy individuals

BACKGROUND: The extent to which sustained caloric restriction (CR) in healthy non-obese adults is safe has not been previously investigated. OBJECTIVE: Assess the safety and tolerability of sustained two-year CR intervention in healthy, non-obese adults. DESIGN: A multi-center, randomized controlled trial. Participants were randomized using a 2:1 allocation in favor of 25% CR vs. Ad-Libitum intake (AL). Adverse and serious adverse events (AE, SAE), safety laboratory tests, and other safety parameters were closely monitored. RESULTS: Three participants were withdrawn from the CR intervention because of the safety concerns. No deaths and one SAE was reported by participants in the CR group. Although the difference in AE between AL and CR groups was not significant, within the CR group, the incidence of nervous system (p = 0.02), musculoskeletal (p = 0.02) and reproductive system (p = 0.002) disorders was significantly higher in the normal-weight than in the overweight participants. At months 12 and 24, bone mineral densities at the lumbar spine, total hip, and femoral neck of participants in the CR group were significantly lower than in those in the AL group. CONCLUSIONS: Two-years of CR at levels achieved in CALERIE was safe and well tolerated. Close monitoring for excessive bone loss and anemia is important

Elevated body mass index and intermediate-term clinical outcomes after acute coronary syndromes

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldPURPOSE: Obesity is a coronary disease risk factor, but its independent effect on clinical outcomes following acute coronary syndromes has not been quantified. We evaluated the relationship between elevated body mass index (BMI) and 30-day, 90-day, and 1-year clinical outcomes postacute coronary syndromes. SUBJECTS AND METHODS: Using 15 071 patients (normal weight [BMI = 18.5-24.9 kg/m(2)], overweight [BMI = 25-29.9 kg/m(2)], obese [BMI = 30-34.9 kg/m(2)] or very obese [BMI > or =35 kg/m(2)]) randomized from 1997-1999 in the SYMPHONY (Sibrafiban vs aspirin to Yield Maximum Protection from ischemic Heart events postacute cOroNary sYndromes) and 2nd SYMPHONY trials, we evaluated the relationships between BMI and 30-day, 90-day, and 1-year mortality and 30-day and 90-day death or myocardial infarction. RESULTS: Increasing BMI was associated with younger age, multiple comorbidities, and greater cardiac medication and procedure use; however, systolic function and coronary disease extent were similar for all BMI categories. Unadjusted Kaplan-Meier mortality estimates were higher for normal-weight patients than for all other BMI groups. After multivariable adjustment, the 30-day mortality hazard ratios (95% confidence interval [CI]) were: overweight, 0.66 (95% CI: 0.47 to 0.94); obese, 0.61 (95% CI: 0.39 to 0.97); very obese, 0.89 (95% CI: 0.48 to 1.64). Adjusted hazard ratios were similar for 90-day and 1-year mortality. There were no statistically significant differences among BMI groups in 30-day and 90-day death or myocardial infarction (unadjusted or adjusted). CONCLUSION: Overweight and obese BMI classifications were associated with better intermediate-term survival after acute coronary syndromes than normal weight and very obese, but death or myocardial infarction rates were similar. Further study is required to understand the apparent association of overweight and moderate obesity with better intermediate-term outcomes

Early statin initiation and outcomes in patients with acute coronary syndromes.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldCONTEXT: The secondary prevention benefit of therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has been clearly demonstrated; however, the role of early initiation of statins after acute coronary syndromes (ACSs) is unknown. OBJECTIVE: To evaluate the association of early statin initiation (< or = 7 days) after ACS with 90-day and 1-year outcomes. DESIGN: Observational cohort from databases of 2 randomized clinical trials, SYMPHONY and 2nd SYMPHONY. SETTING: Nine hundred thirty-one clinical centers in 37 countries. PATIENTS: A total of 12,365 ACS patients randomized from August 1997 to August 1999 who were not taking statins prior to the index ACS and who either started statin therapy early (median, 2.0 [interquartile range, 1.0-3.1] days after ACS; n = 3952) or survived more than 5 days after ACS and never received statin therapy (n = 8413). MAIN OUTCOME MEASURES: Ninety-day incidence of death; death or myocardial infarction (MI); and death, MI, or severe recurrent ischemia; as well as 1-year incidence of death. RESULTS: Ninety-day and 1-year unadjusted mortality comparison suggested early statin benefit (1.2% for early statins vs 2.1% for no statins; hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.42-0.81 for 90-day comparisons and 2.3% for early statins vs 4.4% for no statins; HR, 0.52; 95% CI, 0.40-0.68 for 1-year comparison). However, no benefit was evident for 90-day death or MI (6.5% vs 6.9%; HR, 0.95; 95% CI, 0.82-1.11) or death, MI, or severe recurrent ischemia (9.2% vs 8.9%; HR, 1.04; 95% CI, 0.92-1.18). After propensity and covariate adjustment, there were no 90-day or 1-year differences between the early-statin group and the no-statin group. The 90-day adjusted HR for death was 1.08 (95% CI, 0.75-1.56); for death or MI, 1.08 (95% CI, 0.91-1.29); and for death, MI, or severe recurrent ischemia, 1.15 (95% CI, 0.99-1.34). One-year mortality-adjusted HR was 0.99 (95% CI, 0.73-1.33). Among 2711 patients with core laboratory lipid analysis, early statin was associated with higher adjusted risk for death or death or MI at cholesterol levels below treatment guidelines but was more favorable at higher levels. CONCLUSIONS: In this study, there was no relationship between early initiation of statin therapy and improved outcomes although our subset analysis suggests that outcomes after early statin initiation may vary with cholesterol levels. Confirmation of early treatment effects of statins on outcomes awaits the results of adequately powered randomized clinical trials

Body-composition changes in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE)-2 study: A 2-y randomized controlled trial of calorie restriction in nonobese humans

Background: Calorie restriction (CR) retards aging and increases longevity in many animal models. However, it is unclear whether CR can be implemented in humans without adverse effects on body composition.Objective: We evaluated the effect of a 2-y CR regimen on body composition including the influence of sex and body mass index (BMI; in kg/m2) among participants enrolled in CALERIE-2 (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy), a multicenter, randomized controlled trial.Design: Participants were 218 nonobese (BMI: 21.9-28.0) adults aged 21-51 y who were randomly assigned to 25% CR (CR, n = 143) or ad libitum control (AL, n = 75) in a 2:1 ratio. Measures at baseline and 12 and 24 mo included body weight, waist circumference, fat mass (FM), fat-free mass (FFM), and appendicular mass by dual-energy X-ray absorptiometry; activity-related energy expenditure (AREE) by doubly labeled water; and dietary protein intake by self-report. Values are expressed as means ± SDs.Results: The CR group achieved 11.9% ± 0.7% CR over 2-y and had significant decreases in weight (-7.6 ± 0.3 compared with 0.4 ± 0.5 kg), waist circumference (-6.2 ± 0.4 compared with 0.9 ± 0.5 cm), FM (-5.4 ± 0.3 compared with 0.5 ± 0.4 kg), and FFM (-2.0 ± 0.2 compared with -0.0 ± 0.2 kg) at 24 mo relative to the AL group (all between-group P < 0.001). Moreover, FFM as a percentage of body weight at 24 mo was higher, and percentage of FM was lower in the CR group than in the AL. AREE, but not protein intake, predicted preservation of FFM during CR (P < 0.01). Men in the CR group lost significantly more trunk fat (P = 0.03) and FFM expressed as a percentage of weight loss (P < 0.001) than women in the CR group.Conclusions: Two years of CR had broadly favorable effects on both whole-body and regional adiposity that could facilitate health span in humans. The decrements in FFM were commensurate with the reduced body mass; although men in the CR group lost more FFM than the women did, the percentage of FFM in the men in the CR group was higher than at baseline. CALERIE was registered at clinicaltrials.gov as NCT00427193